Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder

Abstract

Background: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.

Methods: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.

Results: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.

Conclusions: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Figure 1.. Randomization and Follow-up of the Participants.

The primary outcome was the least-squares mean change in the score on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW).

Figure 2.. Scores on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale (ABC-mSW) over 24 Weeks.

Shown are raw mean scores on the ABC-mSW subscale across the 24-week trial of intranasal oxytocin as compared with placebo. Scores on the ABC-mSW range from 0 to 39, with higher scores indicating less social interaction. I bars indicate 95% confidence intervals. Values are offset from each other at each time point for readability. A graph showing least-squares mean changes from baseline in the ABC-mSW subscale scores (primary outcome) is provided in Figure S1. The changes between baseline and each time point that are based on the mean raw values differ from the least-squares mean change from baseline values at each time point because the least-squares mean values are adjusted for the baseline value of the ABC-mSW for each participant at each time point.